title: Persistent factor VIII inhibitors and orthopaedic complications in children with severe haemophilia A.
abstract: Persistence of inhibitors against factor VIII (FVIII) may be a risk factor that increases physical disability in haemophilia A (HA) patients. This study aimed to evaluate prevalence of FVIII inhibitors in previously treated children with severe HA and the impact of persistent inhibitors on knee joint status and lumbar bone mineral density (BMD). Fifty children with severe HA, FVIII <1%; aged 5-16 years were enrolled in this study; they received plasma-derived FVIII on-demand treatment for 50-250 exposure days (EDs). Inhibitors were checked at basal visit and were followed up for 1 year, using Bethesda assay. Cross-sectional clinical scoring and radiological evaluation of the knee joint (by Arnold-Hilgartner staging and Pettersson score), along with lumbar BMD by Dual Energy X-ray Absorptiometry (DEXA) were performed. Patients with persistent inhibitors for 1 to 5 years, median 2.5 years, were 10 (20%). Six had high titre and none of them had completely normal knees, seven had advanced knee arthropathy and six had low lumbar BMD in comparison to 2 and 8 of the 40 patients without inhibitors respectively (P < 0.05). Persistence of inhibitors for more than 2 years without immuno-prophylaxis was a risk factor for joint damage. Low lumbar BMD was found in 88.9% of patients with stages four and five knee arthropathy and in 66.7% of patients with positive hepatitis C. Severe HA children in this Egyptian study had a relatively low prevalence of persistent FVIII inhibitors, which, if not treated, may increase the risk of knee arthropathy and lumbar osteopenia.
authors.affiliation: Clinical Pathology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: I Y
authors.initials: IY
authors.lastname: Abdel-Messih
authors.forename: D M Mohamed
authors.initials: DM
authors.lastname: Habashy
authors.forename: S G
authors.initials: SG
authors.lastname: Moftah
authors.forename: M S
authors.initials: MS
authors.lastname: ElAlfy
authors.forename: M
authors.initials: M
authors.lastname: El-Alfy
mesh_terms: D015502:Absorptiometry, Photon; D000293:Adolescent; D019774:Blood Coagulation Factor Inhibitors / Q000097:blood*; D015519:Bone Density / Q000502:physiology; D001851:Bone Diseases, Metabolic / Q000503:physiopathology*; D002648:Child; D002675:Child, Preschool; D005169:Factor VIII / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D006467:Hemophilia A / Q000150:complications* / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007592:Joint Diseases / Q000503:physiopathology*; D007719:Knee Joint / Q000000981:diagnostic imaging / Q000473:pathology; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000473:pathology
chemical_list: D019774:Blood Coagulation Factor Inhibitors; D005169:Factor VIII